The specific objectives of this research proposal include: 1) clarification of the initial mechanisms and sequence of loss of compensatory vascular smooth muscle (VSM) tone that occurs during prolonged hemorrhagic hypotensive stress; 2) measurement of changes in the neural, humoral and ionic control underlying such loss; 3) a comparative study of differences in reactivity to circulatory stress of arterial and venous VSM in compensatory (e.g., mesenteric) and non-compensatory (e.g., skeletal and cerebral) vascular beds. Normotensive and spontaneously hypertensive rats will be subjected to prolonged hemorrhagic stress (using both the constant pressure and the normovolemic hypotensive models). VSM properties and variables affecting VSM tension that will be measured both in vivo and in vitro during hypotension include: 1) VSM transmembrane potentials and electrical activity; 2) VSM reactivity and sensitivity (via changes in Em, blood vessel diameters and intraluminal pressure) to perivascular neural stimulation, glucocorticoid administration, suffusion with catecholamines, blocking agents (e.g., tetrodotoxin, ouabain), ions (e.g., K ion, Ca 2 ion and Ca 2 ion blockers (tetracaine and veropamin); 3) endogenous sympathetic efferent activity to VSM; 4) tissue and plasma catecholamines, K ion and Ca 2 ion. Such measurements should help clarify the relative importance and sequence and mechanism of failure of neurogenic, huumoral and related ionic control of VSM tension during prolonged circulatory stress. BIBLIOGRAPHIC REFERENCES: Harder, D.R. and Stekeil, W.J. Effect of Removal of Neurogenic Control upon Mesenteric Venous Membrane Potential (Em) in Spontaneously Hypertensive Rats. Lombard, J.H., Loegering, D.J. and Steikiel, W.J. Effects of Prolonged Hemorrhagic Hypotensive Stress on Catecholamine Concentration of Mesenteric Blood Vessels. Blood Vessels, 1977, in press.